It should also be noted that the sensor element described in the U.S. Pat. No. 5,337,747 would not work according to its intentions. This is caused by the fact that more than 99% of the capacitance measured will be caused by the mounting between the membrane (10) and the other electrode (12) which is fixed and is not changing with changing pressure in the chamber. Less than 1% of the total capacitance will be modulated by the deflection of the pressure sensitive membrane.
In the U.S. Pat. No. 5,337,747 it is stated that one of the osmotic membranes should be permeable for water, ions and lactic acid, but not for glucose. This should be obtained by designing pores with a diameter of between 0,6 and 0,74 nm. However, this model for membrane behaviour is over-simplified and does not take into account other important effects contributing to the transport properties of the membrane. A membrane with such a cut-off (pore diameter) will not avoid osmotic effects from the stated solutes. This is because both electrical and steric effects will impede and possibly totally stop the transport of solutes. This means that it is impossible to obtain an osmotic pressure from glucose only.
U.S. Pat. No. 6,224,550, by one of the present inventors, May 1, 2001, relies on maintaining a similar osmolality on both sides of an osmotic membrane. This is obtained by allowing water to flow freely through the membrane and thereby changing the volume (and thereby the concentration) of the “calibrated” fluid inside the sensor. One of the disadvantages with this design is the fact that a significant amount of water must be transported through the membrane when the osmolality in the body is changing. However, only limited fluxes are possible through such membranes, which means that a relatively large area of the osmotic membrane is needed. In addition, the time response will depend on the actual position of a piston, and as such, the sensor will also be non-linear.
Another problem is the friction between the moving piston and the wall. To be able to move the piston, the pressure force must exceed the friction force. From measurements it is seen that even with a large cylinder radius, it is needed a high difference in osmotic pressure to move the piston, which is very unfavourable from the point of accuracy.
A more fundamental problem with this sensor is the fact that to obtain a “calibrated” fluid, the small electrolytes must be allowed to pass through the membrane. As glucose and larger molecules are excluded from passing through the membrane, the “calibrated” fluid will always have to maintain a higher concentration of the electrolytes (chlorine, potassium, etc). The result is an unstable element, from which the electrolytes gradually will be drained out, and in the end the calibrated fluid will disappear.
Osmosis
The principle of the sensor according to the present invention is based on osmosis. In its simplest form, osmosis is the transport of a solvent across a semipermeable membrane caused by differences in the concentration of solutes on either side of the membrane. Osmosis is a process where certain kinds of molecules in a liquid are preferentially blocked by a “semipermeable” membrane. The solvent (in our case water) is diffusing through the membrane into the more concentrated solution, more so than in the opposite direction. The result is a combination of two effects. One is that an osmotic (hydrostatic) pressure is built up in the volume of higher concentration. The other is the reduction in the concentration difference caused by the increased volume of solvent.
Ultimately, a dynamic equilibrium is reached, in which the increase in chemical potential caused by the osmotic pressure difference (□), equals the corresponding change caused by the difference in concentration (C). At osmotic equilibrium, the chemical potential of the solvent must equate the chemical potential of the pure solvent. The ratio between change in pressure versus change in concentration depends on the compliance of the volumes and can be changed (and optimised) by the design.
Osmotic pressure is one example of a colligative property, that is a property which depends only on the number of solute molecules, and not on the nature of the molecules. For relatively small concentrations, as those observed in the body, the osmotic pressure is equal to the pressure that the solute molecules would exert given they were in a gas of the same concentration.
  Π  =      i    ⁢          RT      V      
Where V is the volume of solution containing one mole of solute. The constant i, is the “van't Hoff factor”, which is a measure of the relative increase in amount of entities (particles) due to dissociation.
The present invention can be utilised to monitor any changes within the in chemistry in vivo. The type of solutes and their concentration observed in vivo gives a tremendous amount of information regarding the physiology of the body, and its condition. By measuring the composition for instance in the interstitial fluid (ISF), a lot of information can be obtained regarding de-hydration of the body and different diseases. These are amongst others: diabetes, kidney function etc. Also normal variations for instance in lactate concentration caused by physical activity can be monitored.
In addition to the substances mentioned above, which can change the osmolality in the body, one can also find substances by medication, which give an osmotic contribution in the body fluid. In this case, the present invention can be used to monitor the amount of medication.
Measurement of glucose in ISF is becoming recognised as an alternative to measuring the glucose directly in the blood. The glucose measurement in blood is associated with several drawbacks. It needs a sample of blood, drawn from the body. Even though the equipment has become more sensitive, and therefore requires less blood, the process is associated with pain and the number of tests typically limited to less than 10 per day. It is also known that large variations in measured values can be caused by the measurement procedure.
The present invention is concerned with a variety of parameters like de-hydration, lactic-acid, and amino-acids in addition to glucose.